Senile dementia has become a serious medical and social problem along with the rapid aging of society in recent years and the development of effective anti-dementia drugs has been greatly desired. There are already very many studies on Alzheimer's disease but the cause of the disease has not been clearly defined. Drugs such as acetylcholinesterase inhibitors including donepezil (Aricept (registered trademark)), galantamine (Reminyl) and rivastigmine (Exelon/Rivastach), and NMDA receptor antagonists including memantine hydrochloride (Memary) have been used as Alzheimer's therapeutic drugs. These drugs are very useful as symptomatic therapy but are not drugs for fundamental treatment.
Alzheimer's disease is considered to be caused by aggregation of Aβ, aggregation of tau, and the like. Hence, a substance that inhibits aggregation of these proteins could be used as a fundamental therapeutic drug for Alzheimer's disease.
Yang et al. have reported that curcumin has an Aβ aggregation inhibitory activity, a disaggregation activity on Aβ aggregate, and the like (Non Patent Literature 1). The inventors of the present invention have revealed that curcumin and its derivatives have an inhibitory activity against secretase, which is involved in the generation of Aβ (Patent Literature 1 and 2). Narlawar et al. have synthesized curcumin derivatives by replacing the 1,3-dicarbonyl moiety with a pyrazole ring and reported that these compounds have a tau aggregation inhibitory activity (Non Patent Literature 2).